rs201067092
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBP6
The NM_022124.6(CDH23):c.6026T>A(p.Leu2009His) variant causes a missense change. The variant allele was found at a frequency of 0.0000434 in 1,613,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L2009F) has been classified as Uncertain significance.
Frequency
Consequence
NM_022124.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH23 | NM_022124.6 | c.6026T>A | p.Leu2009His | missense_variant | 46/70 | ENST00000224721.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH23 | ENST00000224721.12 | c.6026T>A | p.Leu2009His | missense_variant | 46/70 | 5 | NM_022124.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000223 AC: 34AN: 152192Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000650 AC: 16AN: 246316Hom.: 0 AF XY: 0.0000523 AC XY: 7AN XY: 133964
GnomAD4 exome AF: 0.0000246 AC: 36AN: 1461122Hom.: 0 Cov.: 32 AF XY: 0.0000248 AC XY: 18AN XY: 726850
GnomAD4 genome ? AF: 0.000223 AC: 34AN: 152192Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74348
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 02, 2016 | The p.Leu2009His variant in CDH23 has been reported in 1 individual with profoun d sensorineural hearing loss who was heterozygous for two pathogenic variants in another gene that likely explained the hearing loss (LMM data). This variant ha s been identified in 7/9042 African chromosomes by the Exome Aggregation Consort ium (ExAC, http://exac.broadinstitute.org; dbSNP rs201067092). Although this var iant has been seen in the general population, its frequency is not high enough t o rule out a pathogenic role. Computational prediction tools and conservation an alyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical s ignificance of the p.Leu2009His variant is uncertain. - |
Usher syndrome type 1 Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at